Recombinant Human PCSK9 Protein (His Tag)

Name: Recombinant Human PCSK9 Protein (His Tag)
Brand: Beta LifeScience
SKU: BLPSN-3670
Availability: InStock

Collections: Antibody / cell therapy targets, Antibody therapeutic / adc target proteins, Recombinant proteins

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Product Overview

Tag	His
Host Species	Human
Accession	AAV67948.1
Synonym	FH3, HCHOLA3, LDLCQ1, NARC-1, NARC1, PC9
Background	Proprotein convertase subtilisin/kexin type 9 (PCSK9), also known as NARC1 (neural apoptosis regulated convertase), which is a newly identified human secretory subtilase belonging to the proteinase K subfamily of the secretory subtilase family. PCSK9 protein is an enzyme which in humans is encoded by the PCSK9 gene with orthologs found across many species. It is expressed in neuroepithelioma, colon carcinoma, hepatic and pancreatic cell lines, and in Schwann cells. PCSK9 protein is highly expressed in the liver and regulates low density lipoprotein receptor (LDLR) protein levels. Inhibition of PCSK9 protein function is currently being explored as a means of lowering cholesterol levels. Thereby, PCSK9 protein is regarded as a new strategy to treat hypercholesterolemia. PCSK9 protein contributes to cholesterol homeostasis and may have a role in the differentiation of cortical neurons. References
Description	A DNA sequence encoding the human PCSK9 (NP_777596.2, with mutation Asp 374 Tyr, natural mutation Val 474 Ile and Gly 670 Glu) (Met 1-Gln 692) was expressed with a His tag at the C-terminus.
Source	HEK293
Predicted N Terminal	Gln 32
AA Sequence	Met 1-Gln 692
Molecular Weight	The recombinant human PCSK9 consists 673 a.a. and predicts a molecular mass of 72.6 kDa.
Purity	>(76.6 + 19.4)% as determined by SDS-PAGE.
Endotoxin	< 1.0 EU per μg protein as determined by the LAL method.
Bioactivity	Measured by its binding ability in a functional ELISA.Immobilized human PCSK9-His(D374Y)at 10 ug/mL (100 uL /well) can bind biotinylated LDLR-His , The EC50 of biotinylated LDLR-His is 0.2-1.4ug/mL.
Formulation	Lyophilized from sterile PBS, pH 7.4.
Stability	The recombinant proteins are stable for up to 1 year from date of receipt at -70°C.
Usage	For Research Use Only
Storage	Store the protein under sterile conditions at -20°C to -80°C. It is recommended that the protein be aliquoted for optimal storage. Avoid repeated freeze-thaw cycles.

Target Details

Target Function	Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.
Subcellular Location	Cytoplasm. Secreted. Endosome. Lysosome. Cell surface. Endoplasmic reticulum. Golgi apparatus. Note=Autocatalytic cleavage is required to transport it from the endoplasmic reticulum to the Golgi apparatus and for the secretion of the mature protein. Localizes to the endoplasmic reticulum in the absence of LDLR and colocalizes to the cell surface and to the endosomes/lysosomes in the presence of LDLR. The sorting to the cell surface and endosomes is required in order to fully promote LDLR degradation.
Protein Families	Peptidase S8 family
Database References	HGNC: 20001 OMIM: 603776 KEGG: hsa:255738 STRING: 9606.ENSP00000303208 UniGene: Hs.18844
Associated Diseases	Hypercholesterolemia, autosomal dominant, 3 (HCHOLA3)
Tissue Specificity	Expressed in neuro-epithelioma, colon carcinoma, hepatic and pancreatic cell lines, and in Schwann cells.

Gene Functions References

The present study shows that serum PCSK9 levels, but not PCSK9 polymorphisms, are associated with coronary artery disease risk in Southern Chinese Han population, and that serum PCSK9 levels are positively associated with AIP PMID: 30205809
In Japanese male subjects, the concentrations of serum PCSK9 and TBIL were correlated with periodontal parameters. PMID: 29516504
C679X loss-of-function PCSK9 variant lowers fasting glucose levels. PMID: 30227170
There was no protective or no deleterious effect of carrying PCSK9 LOF mutations on AD [Alzheimer disease]prevalence nor on age of onset, even when stratified by apolipoprotein E epsilon 4 genotype or by gender. Conclusion: Our data indicate that carrying PCSK9 LOF mutations has a neutral effect on neurocognitive health and the prevalence of AD [Alzheimer disease]. PMID: 29562810
High serum PCSK9 levels predict acute coronary syndrome occurrence at 24-month follow-up after carotid endarterectomy in patients with severe carotid artery stenosis. PMID: 29754909
Taken together, the present study provides evidence of a pro-inflammatory action of PCSK9 on macrophages, mainly dependent by the LDLR. PMID: 29396513
HepG2 cell lines transfected with siRNA directed to PCSK9 were challenged with Hcy, homocysteine thiolactone (HTL), testosterone, 5alpha-dihydroxytestosterone (5alpha-DHT), or estradiol for 24h, leading to an overt expression of PCSK9 and down-regulated expression of LDLR. PMID: 29660344
Plasma PCSK9 levels and lipoprotein distribution are preserved in hypolipoproteinemia carriers. PMID: 29852278
Inverse correlation between PCSK9 and CD36 in hypertrophic adipocytes may be associated with AAA development. PMID: 30210081
Plasma Lp(a) level was associated with PCSK9 in patients with heterozygous familial hypercholesterolemia PMID: 29129821
Authors performed an analysis of public databases and literature for every variant published associated with FH, in the genes LDLR, APOB, and PCSK9. PMID: 29261184
PCSK9 levels increase as glucose metabolism deteriorated. Serum PCSK9 levels positively correlated with 2-hPG (2-h postchallenge plasma glucose) in Chinese Han patients with glucose metabolic diseases. PMID: 29343301
PCSK9i-treated patients had higher rates of cardiovascular comorbidities. PMID: 28849360
PCSK9 overexpression in the aorta may promote acute aortic dissection. PMID: 29197601
High PCSK9 expression is associated with metabolic syndrome. PMID: 28283395
A positive association between plasma PCSK9 concentration and coronary artery calcification in untreated patients with angina-like chest pain was observed in our study, suggesting that further investigation may be needed in order to confirm our primary findings and explore the clinical implications PMID: 28166668
In conclusion, PCSK9 inhibitors such as alirocumab may be an excellent lipid lowering agent in patients with statin intolerance and myotonic dystrophy. PMID: 29056268
Obesity and type 2 diabetes were associated with significantly higher serum levels in young women, but not in young men PMID: 28093849
Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD; phase 2) and RUTHERFORD-2 (phase 3). PMID: 29066265
We present a case of homozygous familial defective apolipoprotein B-100 due to APOB R3500Q (rs5742904) treated with evolocumab ..Identification of a patient homozygous for familial defective apolipoprotein B-100(FDB) and successful treatment with PCSK9 inhibition PMID: 28988723
A complex link between hepatitis C virus infection and PCSK9 has emerged, in which a bidirectional loop of interactions is conceivable. (Review) PMID: 28722331
Genetically determined PCSK9 deficiency might be associated with ectopic fat accumulation. PMID: 28758421
These results suggest that PCSK9 rs7552841 is associated with plasma lipids profiles only in female adolescents, but not in male students. This association can be modified and negated by posttraumatic stress disorder. PMID: 29081489
PCSK9 carriers tended to be associated with an increased response to simvastatin therapy PMID: 28851085
PCSK9 polymorphism may affect HIV pathogenesis, particularly in HIV/hepatitis C coinfected women. A likely mechanism for this effect is PCSK9-mediated regulation of cholesterol metabolism. PMID: 29120899
There was no relationship between plasma PCSK9 levels and arterial stiffness. PMID: 28816230
PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, body weight and an increased risk of type 2 diabetes. PMID: 27908689
ABGL4, LRP8 and PCSK9 polymorphisms and gene interactions increase cardiometabolic risk. PMID: 27853278
these results provide insights into a novel coordinated interplay among three important molecular players in lipid homeostasis - circulating miR-24, miR-223 and PCSK9 - whose regulation is affected by HCV infection and treatment-based viral cure. PMID: 28864162
The present study aimed to explore the direct toxicity of proprotein convertase subtilisin/kexin type 9 (PCSK9) to atherosclerosis (AS) and its association with apoptotic endothelial cells. PMID: 28656218
The minor allele frequency of the PCSK9 A443T, I474V, E670G, and C679X polymorphisms in healthy and malaria-infected Malian children was 0.12, 0.20, 0.26, and 0.02, respectively. 17.6% of subjects carried two of the four SNPs examined. Carriers of the minor allele of the E670G PCSK9 polymorphism might be more susceptible to severe malaria. PMID: 29447211
Circulating PCSK9 concentration as a continuous variable was not significantly associated with the risk of cardiovascular events. More well-designed studies are needed to clarify the role of PCSK9 in cardiovascular risk. PMID: 28413188
Data indicate that the elevation in plasma apoB-48 levels associated with FH is independent of PCSK9 levels. PMID: 28619117
we discuss current experimental and clinical evidence of the role of PCSK9 and its inhibition on lipid metabolism and several pathologic conditions with a focus on clinical outcomes--{REVIEW} PMID: 27533061
The E670G polymorphism of the PCSK9 gene is associated with the lipid levels and risk for coronary heart disease. PMID: 28981947
Here, we assess the available evidence for the association of PCSK9 status with the incidence and control of diabetes mellitus in preclinical and clinical studies, and identify molecular mechanisms regulating PCSK9 expression in the diabetic state. [Review] PMID: 28111330
These results demonstrated the molecular mechanisms of how HCV modulates PCSK9 promoter activity and advanced our understanding on the mutual interactions between HCV and PCSK9. PMID: 29397939
These findings provide useful information for researchers interested in the fields of PCSK9 genetics and cardiovascular risk prediction not only for designing future studies, but also for clinical and public health applications PMID: 28606094
Circulating PCSK9 is significantly related to arterial stiffness, independent of sex and menopausal status in women. PMID: 28468788
Study demonstrated PCSK9 as a direct target of miR-224 and increased miR-224 or decreased PCSK9 could promote apoptosis and suppress proliferation, invasion of tumor cell line in pancreatic neuroendocrine neoplasms. PMID: 28036293
There are no associations between PCSK9 levels and either glucose or lipid homeostasis parameters. Nevertheless, a statistically significant link was observed between PCSK9 and markers of insulin homeostasis, solely in CF patients who presented normal glucose tolerance. PMID: 28447578
PCSK9 interacts with heparan sulfate proteoglycans.Heparan sulfate proteoglycans binding is required for PCSK9-induced LDLR degradation. PMID: 28894089
The results of this study suggest that these biomarker PCSK9 can serve as a potential non-invasive early diagnosis platform reflecting PiB-PET imaging for Mild Cognitive Impairment and Alzheimer's Disease. PMID: 27392853
PCSK9 is not altered specifically in PCOS. PMID: 29109005
A high-throughput time-resolved fluorescence resonance energy transfer assay for autocleavage has been developed using a PCSK9 monoclonal antibody that is sensitive to the conformational changes that occur upon maturation of the proprotein. PMID: 27412534
These studies provide a definitive characterization of the composition and activity of the truncated form of PCSK9 found in human serum PMID: 24776539
PCSK9 loss-of-function variants were associated with a pooled odds ratio for coronary heart disease of 0.51 in blacks and 0.82 in whites. PMID: 28768753
Mature PCSK9 associated with atheroma volume and impaired vessel remodeling in HeFH patients with coronary artery disease PMID: 28502498
Despite having lower LDL-C, circulating PCSK9 levels were increased in patients coinfected with HIV and HCV in parallel with elevations in the inflammatory, proatherogenic cytokine interleukin-6. PMID: 27130349
Circulating PCSK9 is associated with New-onset diabetes after transplantation (NODAT) in renal transplant recipients. The PCSK9 pathway may contribute to the pathogenesis of NODAT. PMID: 28461454

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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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